ID A0A4R5DWF2_9ACTN Unreviewed; 564 AA. AC A0A4R5DWF2; DT 31-JUL-2019, integrated into UniProtKB/TrEMBL. DT 31-JUL-2019, sequence version 1. DT 18-SEP-2019, entry version 2. DE RecName: Full=CTP synthase {ECO:0000256|HAMAP-Rule:MF_01227}; DE EC=6.3.4.2 {ECO:0000256|HAMAP-Rule:MF_01227}; DE AltName: Full=Cytidine 5'-triphosphate synthase {ECO:0000256|HAMAP-Rule:MF_01227}; DE AltName: Full=Cytidine triphosphate synthetase {ECO:0000256|HAMAP-Rule:MF_01227}; DE Short=CTP synthetase {ECO:0000256|HAMAP-Rule:MF_01227}; DE Short=CTPS {ECO:0000256|HAMAP-Rule:MF_01227}; DE AltName: Full=UTP--ammonia ligase {ECO:0000256|HAMAP-Rule:MF_01227}; GN Name=pyrG {ECO:0000256|HAMAP-Rule:MF_01227}; GN ORFNames=E1289_36460 {ECO:0000313|EMBL:TDE16944.1}; OS Actinomadura sp. 6K520. OC Bacteria; Actinobacteria; Streptosporangiales; Thermomonosporaceae; OC Actinomadura. OX NCBI_TaxID=2530364 {ECO:0000313|EMBL:TDE16944.1, ECO:0000313|Proteomes:UP000295189}; RN [1] {ECO:0000313|EMBL:TDE16944.1, ECO:0000313|Proteomes:UP000295189} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=6K520 {ECO:0000313|EMBL:TDE16944.1, RC ECO:0000313|Proteomes:UP000295189}; RA Sahin N., Ay H., Saygin H.; RT "Draft genome sequences of novel Actinobacteria."; RL Submitted (MAR-2019) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Catalyzes the ATP-dependent amination of UTP to CTP with CC either L-glutamine or ammonia as the source of nitrogen. Regulates CC intracellular CTP levels through interactions with the four CC ribonucleotide triphosphates. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O + L-glutamine + UTP = ADP + CTP + 2 H(+) + L- CC glutamate + phosphate; Xref=Rhea:RHEA:26426, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:37563, ChEBI:CHEBI:43474, ChEBI:CHEBI:46398, CC ChEBI:CHEBI:58359, ChEBI:CHEBI:456216; EC=6.3.4.2; CC Evidence={ECO:0000256|HAMAP-Rule:MF_01227, CC ECO:0000256|SAAS:SAAS01116648}; CC -!- ACTIVITY REGULATION: Allosterically activated by GTP, when CC glutamine is the substrate; GTP has no effect on the reaction when CC ammonia is the substrate. The allosteric effector GTP functions by CC stabilizing the protein conformation that binds the tetrahedral CC intermediate(s) formed during glutamine hydrolysis. Inhibited by CC the product CTP, via allosteric rather than competitive CC inhibition. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo CC pathway; CTP from UDP: step 2/2. {ECO:0000256|HAMAP-Rule:MF_01227, CC ECO:0000256|SAAS:SAAS00710815}. CC -!- SUBUNIT: Homotetramer. {ECO:0000256|HAMAP-Rule:MF_01227, CC ECO:0000256|SAAS:SAAS00710816}. CC -!- MISCELLANEOUS: CTPSs have evolved a hybrid strategy for CC distinguishing between UTP and CTP. The overlapping regions of the CC product feedback inhibitory and substrate sites recognize a common CC feature in both compounds, the triphosphate moiety. To CC differentiate isosteric substrate and product pyrimidine rings, an CC additional pocket far from the expected kinase/ligase catalytic CC site, specifically recognizes the cytosine and ribose portions of CC the product inhibitor. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- SIMILARITY: Belongs to the CTP synthase family. CC {ECO:0000256|HAMAP-Rule:MF_01227, ECO:0000256|SAAS:SAAS00710794}. CC -!- CAUTION: Lacks conserved residue(s) required for the propagation CC of feature annotation. {ECO:0000256|HAMAP-Rule:MF_01227}. CC -!- CAUTION: The sequence shown here is derived from an CC EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is CC preliminary data. {ECO:0000313|EMBL:TDE16944.1}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; SMLC01000309; TDE16944.1; -; Genomic_DNA. DR UniPathway; UPA00159; UER00277. DR Proteomes; UP000295189; Unassembled WGS sequence. DR CDD; cd01746; GATase1_CTP_Synthase; 1. DR Gene3D; 3.40.50.880; -; 1. DR HAMAP; MF_01227; PyrG; 1. DR InterPro; IPR029062; Class_I_gatase-like. DR InterPro; IPR004468; CTP_synthase. DR InterPro; IPR017456; CTP_synthase_N. DR InterPro; IPR017926; GATASE. DR InterPro; IPR033828; GATase1_CTP_Synthase. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR11550; PTHR11550; 1. DR Pfam; PF06418; CTP_synth_N; 1. DR Pfam; PF00117; GATase; 1. DR SUPFAM; SSF52317; SSF52317; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR TIGRFAMs; TIGR00337; PyrG; 1. DR PROSITE; PS51273; GATASE_TYPE_1; 1. PE 3: Inferred from homology; KW ATP-binding {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710699}; KW Complete proteome {ECO:0000313|Proteomes:UP000295189}; KW Glutamine amidotransferase {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|PROSITE-ProRule:PRU00605, ECO:0000256|SAAS:SAAS00710676}; KW Ligase {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710762, ECO:0000313|EMBL:TDE16944.1}; KW Magnesium {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710689}; KW Metal-binding {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710675}; KW Nucleotide-binding {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710810}; KW Pyrimidine biosynthesis {ECO:0000256|HAMAP-Rule:MF_01227, KW ECO:0000256|SAAS:SAAS00710748}. FT DOMAIN 302 551 Glutamine amidotransferase type-1. FT {ECO:0000259|PROSITE:PS51273}. FT NP_BIND 24 29 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 158 160 Allosteric inhibitor CTP. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 198 203 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT NP_BIND 198 203 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT REGION 1 277 Amidoligase domain. {ECO:0000256|HAMAP- FT Rule:MF_01227}. FT REGION 393 396 L-glutamine binding. {ECO:0000256|HAMAP- FT Rule:MF_01227}. FT ACT_SITE 392 392 Nucleophile. {ECO:0000256|PROSITE- FT ProRule:PRU00605}. FT ACT_SITE 392 392 Nucleophile; for glutamine hydrolysis. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT ACT_SITE 524 524 {ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605}. FT ACT_SITE 526 526 {ECO:0000256|HAMAP-Rule:MF_01227, FT ECO:0000256|PROSITE-ProRule:PRU00605}. FT METAL 81 81 Magnesium. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT METAL 151 151 Magnesium. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 23 23 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 23 23 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 81 81 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 234 234 Allosteric inhibitor CTP; alternate. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 234 234 UTP; alternate. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 252 252 ATP. {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 365 365 L-glutamine; via carbonyl oxygen. FT {ECO:0000256|HAMAP-Rule:MF_01227}. FT BINDING 416 416 L-glutamine. {ECO:0000256|HAMAP-Rule: FT MF_01227}. FT BINDING 477 477 L-glutamine; via amide nitrogen. FT {ECO:0000256|HAMAP-Rule:MF_01227}. SQ SEQUENCE 564 AA; 61419 MW; DBCF46F85919B078 CRC64; MPSAATGSSR PTKHLFVTGG VASSLGKGLT ASSLGRLLTL RGLRVTMQKL DPYLNVDPGT MNPFQHGEVF VTDDGAETDL DIGHYERFLD TELHGSANVT TGQVYSNVIA KERRGEYLGD TVQVIPHITN EIKDRIIGMA ADDDVDIVIT EVGGTVGDIE SLPFLEAVRQ IRHEIGRDNC FFLHVSLLPY IGPSGELKTK PTQHSVAALR SIGIQPDAIV CRSDRPITDG LKHKISLMCD VDREAVVSAV DAASIYDIPK VLHSEGLDAY VVRRLDLPFR DVDWGAWDEL LRRVHKPARE VTIALVGKYI DLPDAYLSVT EALRHGGFGN DAKVHIRWVK SDDCETAEGA KRELDGVDGV LIPGGFGVRG IEGKLGAVRH ARENRVPLLG ICLGLQCMVI EAARTLAGLA GADSAEFDAT TAHPVVATMT DQVDVVAGER DMGGTMRLGL YPADLAEGSI VRELYGEAKV SERHRHRYEV SNVYRDRLEE AGLWFSGLSP DGRLVEYVEL PRDRHPFFVG TQAHPEFRSR PTRPHPLFTG LVTAALDYAE ARTGDGEAGN VTVS //